Distinct Morphological Types of Small Airway Obstructions in Smokers with Emphysema and End-Stage COPD

The precise nature of small airway obstructions in COPD remains poorly understood, especially at early disease stages. This study aimed to characterize small airway obstructions and numbers up to the terminal bronchioles (TB) in smokers with limited emphysema and end-stage COPD. We hypothesized that obstruction subtypes would differ in morphology, nature and number from early to end-stage COPD. Whole lungs from seven donors (Control: declined for extrapulmonary reasons), eight donors (history of smoking), of which three had 5% emphysema (smokers with emphysema, SE) and eight end-stage COPD patients were inflated and processed. MicroCT of tissue was used to assess number of TB, aerated TB, number and type of obstructions and cross-correlated with histopathology. Obstructions were mainly present in SE and COPD resulting in less aerated TB. Based on emphysema extent, more non-aerated TB were present in regions with no emphysema compared to mild emphysema, however, destruction was more prominent in mild emphysema. Multiple types of obstructions comprising occlusions, webs and collapses were identified. In SE, obstructions primarily comprised webs and occlusions, while all obstruction types were present in COPD. On histopathology, obstructions were identified as mucus plugs. Multiple types of obstruction characterized as mucus plugs were identified in SE and end-stage COPD. Their morphology, nature and number evolved from SE to end-stage COPD. A shift from obstruction-dominant dysfunction to destruction-dominant pathology was found in smokers based on emphysema presence. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).